Fig. 1: HIF-2α mRNA is overexpressed in ccRCC cells.

a Expression qPCR analysis for HIF-2α mRNA in tissue lysates from renal tumors or corresponding normal kidney tissue from the Erlangen RCC cohort (ccRCC: clear cell renal carcinoma [n = 114], pRCC: papillary renal cell carcinoma [n = 16], chRCC: chromophobe renal cell carcinoma [n = 11]). Data shown are median and interquartile range. Significance was tested by two-way ANOVA followed by Bonferroni’s post hoc test. b RNA-seq expression values for HIF-2α in different renal tumors and corresponding normal kidney tissue from the TCGA KIRC (n = 72), KIRP (n = 31) and KICH (n = 23) data sets. Median and interquartile range. P-values were determined by two-way ANOVA followed by Bonferroni’s post hoc test. c RNAscope experiment for HIF-2α mRNA in ccRCC tissue. Arrows indicate HIF-2α mRNA transcripts in tumor cells. V = vessel. Scale bars, 100 µm or 75 µm as indicated. Representative image from independent samples of seven different patients with similar results. d Log₂ fold change of HIF-related genes in snRNA-seq data comparing tumor cells from 30 ccRCC samples versus proximal tubule (PT) cells from four adjacent kidney tissue samples²⁹. Only samples with significantly differentially expressed transcripts are shown (adjusted p < 0.05, average log₂ fold change ≠ 0). e Isolation of renal tumor cells and corresponding tubule cells from non-diseased tissue of tumor nephrectomy specimens. Created in BioRender. Naas, S. (2025) https://BioRender.com/c87s173. f Immunoblot analyses for HIF-1α, HIF-2α, pVHL, and β-actin in lysates from primary tubule (PTC) and tumor (ccRCC) cells isolated from tissue specimens of patient #1. Representative blot from 19 independent experiments with similar results. g Expression qPCR analysis for HIF-2α mRNA in lysates from primary tubule cells (PTC) and primary tumor (ccRCC) isolated from 34 different individuals. Graph shows median with interquartile range and p-values from a two-tailed unpaired t-test.